title: Drug residue formation from ronidazole, a 5-nitroimidazole. I. Characterization of in vitro protein alkylation.
abstract: The metabolic activation of [14C]ronidazole by rat liver enzymes to metabolite(s) bound to macromolecules was investigated. The alkylation of protein by [14C]ronidazole metabolite(s) was catalyzed most efficiently by rat liver microsomes, in the absence of oxygen utilizing NADPH as a source of reducing equivalents. Based on a comparison of total ronidazole metabolized versus the amount bound to microsomal protein, approximately one molecule alkylates microsomal protein for every 20 molecules of ronidazole metabolized. Protein alkylation was strongly inhibited by sulfhydryl-containing compounds such as cysteine and glutathione whereas methionine had no effect. Based on HPLC analysis of ronidazole, cysteine was found not to inhibit  microsomal metabolism of ronidazole ruling out a decrease in the rate of production of the reactive metabolite(s) as the mechanism of cysteine inhibition.
mesh_terms: D000478:Alkylation; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000378:metabolism; D005260:Female; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D009593:Nitroimidazoles / Q000378:metabolism*; D009696:Nucleic Acids / Q000378:metabolism; D009711:Nucleotides / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D012385:Ronidazole / Q000378:metabolism*; D013552:Swine
chemical_list: D009593:Nitroimidazoles; D009696:Nucleic Acids; D009711:Nucleotides; D009243:NAD; D009249:NADP; D012385:Ronidazole; D009251:NADPH-Ferrihemoprotein Reductase; D003545:Cysteine